LncRNA SNHG17 knockdown promotes Parkin-dependent mitophagy and reduces apoptosis of podocytes through Mst1

Cell Cycle. 2020 Aug;19(16):1997-2006. doi: 10.1080/15384101.2020.1783481. Epub 2020 Jul 5.

Abstract

LncRNAs play important roles in the regulation of podocyte apoptosis in diabetic nephropathy (DN). However, the role of lncRNA SNHG17 in controlling mitophagy-induced apoptosis of podocytes in DN is unknown. This study aims to elucidate the underlying mechanism of lncRNA SNHG17 in the regulation of mitophagy-induced apoptosis of podocytes in DN. LncRNA SNHG17 and Mammalian Sterile 20-like kinase 1 (Mst1) expression were upregulated in glomeruli and podocytes of DM mice and high glucose-treated podocytes, whereas Parkin expression was downregulated. LncRNA SNHG17 overexpression suppressed mitophagy and induced apoptosis of podocytes while silencing lncRNA SNHG17 promoted mitophagy and reduced the apoptosis of podocytes. In addition, lncRNA SNHG17 interacted with Mst1 and regulated the degradation of Mst1. We further found lncRNA SNHG17 regulated Parkin expression through Mst1. Mechanistically, lncRNA SNHG17 regulated Parkin-dependent mitophagy and apoptosis of podocytes through regulating Mst1. Finally, silencing lncRNA SNHG17 promoted mitophagy and relieved DNin vivo. In conclusion, lncRNA SNHG17 knockdown promotes Parkin-dependent mitophagy and reduces apoptosis of podocytes through regulating the degradation of Mst1.

Keywords: Mst1; Parkin; apoptosis; diabetic nephropathy; lncRNA SNHG17; mitophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / pathology
  • Gene Knockdown Techniques*
  • Male
  • Mice, Inbred C57BL
  • Mitophagy / genetics*
  • Podocytes / metabolism
  • Podocytes / pathology*
  • Protein Serine-Threonine Kinases / metabolism*
  • Proteolysis
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • RNA, Long Noncoding
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Stk4 protein, mouse
  • Protein Serine-Threonine Kinases

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China [Grant No.81600647 to F.Guo; Grant No. 81700138 to Wm.Wang], and the Key Scientific Research Project of Universities in Henan Province [Grant No. 20A320013 to F.Guo] and Young Foundation of the First Affiliated Hospital of Zhengzhou University (to F. Guo).